1. Field of the Invention
The present invention relates to a process for recovering L-phenylalanine (hereinafter abbreviated as L-Phe) as its monomethyl sulfate salt at high yield.
2. Description of the Background
L-phenylalanine and the methyl ester thereof, L-phenylalanine methyl ester (hereinafter abbreviated as L-PM) are important raw materials for peptide synthesis. Particularly, there is a great demand for them as raw materials for a dipeptide sweetener, .alpha.-L-aspartyl-L-phenylalanine methyl ester (hereinafter abbreviated to .alpha.-APM) .
Formerly, various processes for the production of .alpha.-APM have been studied. The conventional known industrial processes include a process which comprises reacting N-protected L-aspartic anhydride with L-PM (U.S. Pat. No. 3,786,039) and a process which comprises enzymatic condensation of N-benzyloxycarbonyl-L-aspartic acid and L-PM (Japanese Patent Laying-Open No. 92729/1978).
To obtain L-PM in high purity, a conventional method is used wherein L-Phe is esterified with methanol in the presence of an inorganic acid, such as hydrochloric or sulfuric acid, the resulting acidic reaction solution is neutralized with a suitable base in the presence of water, then the released L-PM is extracted with a water-immiscible organic solvent such as toluene. According to this process, the reaction mixture contains dissolved L-Phe, which remains unreacted in the extract aqueous phase after esterification, and L-Phe, which is produced by decomposition of L-PM upon neutralization and extraction.
L-Phe is a relatively expensive material. Accordingly, it is industrially important to recover any residual L-Phe which fails to be converted, and to reuse it as a raw material. For recovery of L-Phe in the extract aqueous phase of the above-described process, for example, it is recovered as L-phenylalanine monomethyl sulfate salt (hereinafter abbreviated as L-Phe.MeSO.sub.4 H) (Japanese Patent Laying-Open No. 247913/1994). In recovering L-Phe.MeSO.sub.4 H, L-tyrosine and D-phenylalanine, which are difficult to efficiently remove as impurities, can be removed with high selectivity by a simple operation and L-Phe.MeSO.sub.4 H of extremely high optical purity is obtained from a crystallization system of L-Phe of low optical purity and monomethyl sulfate (hereinafter abbreviated to MeSO.sub.4 H). Thus, this process is excellent as an industrial recovery of L-Phe.
For example, L-Phe.MeSO.sub.4 H may be separated out by concentration of the extract aqueous phase under acidic conditions when sulfuric acid is used as an acid catalyst. For efficient recovery, however, the aqueous phase should be concentrated to 1/2 to 1/3 the volume. However, such concentration requires the input of a large amount of energy, decreasing the value of recovering the L-Phe.
When L-Phe.MeSO.sub.4 H crystals containing impurities are purified by recrystallization from water or slurry-washing, these highly water soluble crystals, can be lost in the mother liquor, resulting in reduced yield.